Innate immune cell interactions mediated by the SIRP receptor family

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In vertebrates, multiple systems collaborate to ensure recognition and elimination of cells that are aged, defective or infected, while preserving normal “self” tissues. Immune homeostasis requires a balance between activating receptors that promote responses and inhibitory receptors that maintain self-tolerance. The long-term goal of my program is to understand how these activating and inhibitory responses are integrated to maintain accurate self/non-self recognition. This interplay has been studied extensively in lymphocytes that mediate adaptive immunity, but is less well understood in innate immune cells such as macrophages (M?). We have shown that the innate immune receptor Signal Regulatory Protein-α (SIRPα) is an inhibitory receptor that recognizes a protein expressed on virtually all healthy cells. I propose to identify the signalling pathways and down-stream mediators by which SIRPα inhibits M? responses to normal self and is regulated to allow appropriate responses to non-self cells.